Pembrolizumab Plus Bevacizumab and Chemotherapy for ALK-rearranged NSCLC With Persistent 5'ALK (BEYOND)

Bevacizumab and Chemotherapy With or Without Pembrolizumab in First Line Alectinib Failed ALK-rearranged Advanced Lung Adenocarcinoma Patients With Persistent 5'ALK: A Phase II Randmized Control Trial

This is an open-label, multiple centers, two-arms phase II study to evaluate the safety and efficacy Pembrolizumab,Bevacizumab in combination with Chemotherapy could improve PFS in Alectinib Failed ALK-rearranged Advanced Lung Adenocarcinoma with Persistent 5'ALK. The eligible patients should have Stage IV Adenocarcinoma ALK-rearranged tested by NGS Perisitent with 5'ALK Failed from first line Alectinib. The patients should meet the physical requirements to receive Pembrolizumab, Bevacizumab with Chemotherapy. All the patients who meet these requirements will be enrolled in this study. The eligible patients will be treated with Pembrolizumab 200 mg intravenously (IV) plus Bevacizumab 15mg/kg+ Pemetrexed 500mg/m2+Carboplatin AUC=4 for up to 4 cycles followed by Pembrolizumab 200mg Q3W+ Bevacizumab 15mg/kg+Pemetrexed 500mg/m2 for up to 31cycles or until disease progression, intolerable toxicity, or physician or participant decision.

Study Overview

• Status: Recruiting
• Conditions: Lung Adenocarcinoma; ALK Gene Mutation; Immunotherapy
• Intervention / Treatment: Drug: Pembrolizumab injection

Detailed Description

This is an open-label, multiple centers, two-arms phase II study to evaluate the safety and efficacy Pembrolizumab,Bevacizumab in combination with Chemotherapy could improve PFS in Alectinib Failed ALK-rearranged Advanced Lung Adenocarcinoma with Persistent 5'ALK. The eligible patients should have Stage IV Adenocarcinoma ALK-rearranged tested by NGS Perisitent with 5'ALK Failed from first line Alectinib. The patients should meet the physical requirements to receive Pembrolizumab, Bevacizumab with Chemotherapy. All the samples were collected for single-RNA sequencing and DSP to evalutate the TME to predict the efficacy.

• Study Type: Interventional
• Enrollment (Estimated): 78
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Nong C Yang, MD; Phone Number: +8613873123436 +8613873123436; Email: yangnong0217@163.com
• Study Contact Backup: Name: Yongchang C Zhang, MD; Phone Number: 7+861383123436 +8613873123436; Email: zhangyongchang@csu.edu.cn

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410013
      • Recruiting
      • Hunan Cancer hospital
      • Contact: Yongchang Zhang, MD; Phone Number: +86 731 89762323; Email: zhangyongchang@csu.edu.cn
      • Contact: Nong Yang, MD; Phone Number: +86 731 89762321; Email: yangnong0217@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years of age on day of signing informed consent.

  • Stage IV ALK-rearranged Lung Adenocarcinoma Persistent with 5'ALK Failed from first line Alectinib

    • Have at least 1 lesion that meets the criteria for being measurable, as defined by RECIST 1.1, and is appropriate for selection as a target lesion, as determined by local site investigator radiology review. Lesions that appear measurable, but have undergone palliative irradiation, cannot be target lesions ④20 FFPE sliders prepared,Subjects who do not have histology samples (defined as core or excisional biopsy, or resections) will need to undergo a new biopsy to provide a tissue sample ⑤Eastern Cooperative Oncology Group performance status 0 or 1

      • Life expectancy ≥3 months

        • Adequate hematologic and end organ function

Exclusion Criteria:

Cancer-Specific Exclusions:

①Active or untreated central nervous system metastases

②Malignancies other than NSCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome

General Medical Exclusions:

• Pregnant or lactating women.

  • Has active autoimmune disease that has required systemic treatment in the past 2 years.

    • History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.

      • Positive test for human immunodeficiency virus.

        ⑤Active hepatitis B or hepatitis C.

        ⑥Severe infection within 4 weeks prior to randomization .

        ⑦Significant cardiovascular disease.

        ⑧Illness or condition that interferes with the participant's capacity to understand, follow and/or comply with study procedures.

        ⑨Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment for another health-related problem.

Exclusion Criteria Related to Medications: Prior treatment with anti-programmed death-1, anti-PD-L1 therapeutic antibodies，and anti-VEGF agents.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pembrolizumab plus Bevacizumab and Chemotherapy; Pembrolizumab Plus Bevacizumab and Chemotherapy was used for ALK-rearranged NSCLC With Persistent 5'ALK.	Drug: Pembrolizumab injection; Pembrolizumab 20mg ivgtt once every 21day Platium based Chemotherapy ivgtt once every 21day Bevacizumab 15mg/kg ivgtt once every 21day; Other Names: Bevacizumab; pemetrexed; CISPLATIN
Experimental: Bevacizumab plus Chemotherapy; Bevacizumab plus Chemotherapy was used for ALK-rearranged NSCLC With Persistent 5'ALK.	Drug: Pembrolizumab injection; Pembrolizumab 20mg ivgtt once every 21day Platium based Chemotherapy ivgtt once every 21day Bevacizumab 15mg/kg ivgtt once every 21day; Other Names: Bevacizumab; pemetrexed; CISPLATIN

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS	Defined as the time from the beginning of treatment to the first imaging disease progression or death (whichever occurs first)	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	Defined as the proportion of subjects in complete remission (CR) and partial remission (PR) to the total subjects	2 years
DCR	Defined as the proportion of subjects with complete remission (CR), partial remission (PR) and stable disease (SD) to the total subjects	2 years

Collaborators and Investigators

• Sponsor: Hunan Province Tumor Hospital
• Investigators: Principal Investigator: Yongchang C Zhang, MD, Hunan Cancer hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 29, 2024
• Primary Completion (Estimated): November 16, 2026
• Study Completion (Estimated): February 16, 2027

Study Registration Dates

• First Submitted: February 18, 2022
• First Submitted That Met QC Criteria: March 1, 2022
• First Posted (Actual): March 4, 2022

Study Record Updates

• Last Update Posted (Actual): May 30, 2024
• Last Update Submitted That Met QC Criteria: May 28, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Adenocarcinoma; Adenocarcinoma of Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Folic Acid Antagonists; Cisplatin; Pembrolizumab; Pemetrexed
• Other Study ID Numbers: 2022017

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No